ATP The energy currency: Bioenergetics, catabolism

Bioenergetics, catabolism

The energy currency:

ATP

Electrontransfer, the most important electron carriers

NAD: nicotinamide adenine-dinucleotide

Ubiquinone FAD: flavin

adenine-dinucleotide

Terminal oxydation, oxidative phosphorylation Location: inner mitochondrial membrane

Terminal oxidation:

The oxydation of co-factor bonded hydrogen (NADH, FADH₂) to water.

½ O₂ + 2H⁺ + 2e^- H₂O

½ O₂ /H₂O E₀= +0,82 V

NADH + H⁺ /NAD⁺ E₀= -0,32 V DE_o= 1,14 V DG⁰= -220 kJ/mol

Oxydative phosphorylation: The phosphorylation of ADP to ATP The terminal oxidation and the oxydative phosphorylation are

coupled processes.

eukaryotic cells

The structure of mitochondron Length: 2 mm, diameter: 0,5 mm

Origin: the symbiosys of aerobic bacteria and an ancient eukarytotic cell

The number of mitochondria differs in different cell types (e.g.: hepatocyte: 800- 2500 /cell, red blood cell: 0)

Structure: double membrane

-outer membrane: approx.: 50 % lipid, 50% protein, porin channels: permeable for the intermediers of central metabolism

-inner membrane: 75% protein, non-permeable fol almost all ions The link between the

mitochondrial matrix and cytosol is maintained by the transport systems of inner membrane

The respiratory electron transfer chain and the ATP synthase are loceted here too.

matrix

inner membrane

e-

NADH + H⁺ NAD⁺

FADH₂ FAD

O₂ H₂O

+ + + + + +

H⁺

H⁺

ADP

ATP P_i

O₂ + 4e^- + 4H⁺ H₂O

The components of mitochondrial respiratory electron tranfer chain, electron carrier molecules

4 complexes: redox proteins with different prosthetic groups Electron donor: NADH + H⁺ , FADH₂

Electron acceptor: O₂

Electron carrier molecules:

1. Cytochromes: They contain a hem prosthetic group (Fe²⁺ Fe³⁺) They can be shared on the base of their absorption spectra: a, b, c

2. Ubiquinone: benzoquinone

derivative, uptake/release of 1 or 2 electrons.

Prosthetic groups with electron carrier function in the respiratory electron

transfer chain:

FeS: iron-sulfur complexes. They have non-hem iron: Fe²⁺ Fe³⁺

inorganic S, or Cys S connection.

Copper containing proteins: Cu⁺ Cu²⁺

Redox couple redox potential (V)

NAD⁺/NADH + H⁺ -0,32

FAD/FADH₂ -0,21

Ubiquinone/ubiquinol +0,045

Cytochrome_b Fe³⁺/Fe²⁺ +0,08 Cytochrome _c Fe³⁺/Fe²⁺ +0,22 Cytochrome _a Fe³⁺/Fe²⁺ +0,29

½ O₂/H₂O +0,82

ATP synthesizing machinery in the mitochondria

e-

H⁺

H⁺

H⁺ H⁺ H⁺

H⁺

3 H⁺ 3 H⁺

NADH Q

Cyt c

NAD + NADH

Dehydrogenase complex

Cytochrome b-c1 complex

Cytochrome oxydase complex

ADP+P_i ATP ATP

Synthase porins

Intermembrane space

Matrix

e- +O₂

H₂O FADH₂ FAD

I

II

III IV

Complex I: NADH-UQ-oxidoreductase (NADH-dehydrogenase)

A hugh protein complex with 25 subunits. The NADH binding pocket faces to the matrix. Electrons from complex I flow to ubiquinon It has proton pump activity.

Complex II: succinate-UQ-oxidoreductase

It has a FAD prosthetic group. Succinate dehydrogenase (TCA cycle) is a member of complex II. Electrons from complex II flow to ubiquinon. It has no proton pump activity.

DE

> DE

A the difference in redox potential in the FAD/FADH₂ : UQ/UQH₂ redox couples is too low to ride the proton pump.

Glycerol-phosphate dehydrogenase Acyl-CoA dehydrogenase

Other sources of electrons to reduce ubiquinone

ATP synthesizing machinery in the mitochondria

e-

H⁺

H⁺

H⁺ H⁺ H⁺

H⁺

3 H⁺ 3 H⁺

NADH Q

Cyt c

NAD + NADH

Dehydrogenase complex

Cytochrome b-c1 complex

Cytochrome oxydase complex

ADP+P_i ATP ATP

Synthase porins

Intermembrane space

Matrix

e- +O₂

H₂O FADH₂ FAD

I

II

III IV

Complex III: UQH₂-cytochrome c-oxidoreductase Electrons from complex III flow to cytochrome c.

It has proton pump activity.

Complex IV: cytochrome c oxidase O₂ is reduced to water by this complex.

It has proton pump activity.

ATP synthesizing machinery in the mitochondria

e-

H⁺

H⁺

H⁺ H⁺ H⁺

H⁺

3 H⁺ 3 H⁺

NADH Q

Cyt c

NAD + NADH

Dehydrogenase complex

Cytochrome b-c1 complex

Cytochrome oxydase complex

ADP+P_i ATP ATP

Synthase porins

Intermembrane space

Matrix

e- +O₂

H₂O FADH₂ FAD

I

II

III IV

Terminal oxidation (subsequent electron transfers) – exergonic oxidative phosphorylation

(ADP + P_i ATP) – endergonic Coupled reactions

P/O ratio

in case of NADH: 3 in case of FADH₂: 2

ATP synthesizing machinery in the mitochondria

e-

H⁺

H⁺

H⁺ H⁺ H⁺

H⁺

3 H⁺ 3 H⁺

NADH Q

Cyt c

NAD + NADH

Dehydrogenase complex

Cytochrome b-c1 complex

Cytochrome oxydase complex

ADP+P_i ATP ATP

Synthase porins

Intermembrane space

Matrix

e- +O₂

H₂O FADH₂ FAD

I

II

III IV

ATP syntase Consist of 2 units: F₁ and F_o

F₁: responsible for the phosphorylation of ADP, F_o: proton channel Uncoupling agents (e.g.: 2,4-dinitrophenol), uncouple of the

terminal oxidation and oxidative phosphorylation acceptor control

Mitchell’s chemiosmotic theory

proton motor force:

Membrane potential

Delta in H⁺ ion concentration